TCA Toxicity Summary

Critical Features

  • Highly toxic - fatal arrhythmias possible
  • Toxic dose: >15 mg/kg
  • Rapid deterioration possible
  • Observe minimum 6 hours

ECG Findings

  • QRS >120 msec (predicts seizures/arrhythmias)
  • PR and QT prolongation
  • AV block
  • Brugada pattern possible

Anticholinergic Effects

  • Hot, dry skin
  • Dry mouth
  • Dilated pupils
  • Urinary retention
  • Ileus
  • Confusion/drowsiness

Emergency Management

  • Airway protection first
  • Sodium bicarbonate for QRS >120 or hypotension
  • Activated charcoal if <1 hour
  • Benzodiazepines for seizures
  • Fluid resuscitation for hypotension

Investigations

  • ECG (serial)
  • ABG (acid-base status)
  • U&Es, glucose
  • Calcium, magnesium
  • Creatine kinase

Severe Complications

  • Ventricular arrhythmias
  • Cardiogenic shock
  • Status epilepticus
  • Respiratory arrest
  • ARDS
  • Rhabdomyolysis

Critical Care

  • Early ICU referral if unstable
  • Consider glucagon for refractory shock
  • Monitor for sudden deterioration
  • Consider lipid emulsion therapy

Tricyclic Antidepressants Toxicity

Life-threatening poisoning requiring urgent recognition and aggressive management

Overview

Tricyclic antidepressants are highly toxic by ingestion; fatal cardiac arrhythmias may occur soon after ingestion. Toxicity is due to a combination of anticholinergic (antimuscarinic, atropine-like) effects at autonomic nerve endings and in the brain, cardiac sodium channel blockade and alpha 1 adrenergic receptor blockade.

Critical Dose: Ingestion of 15 mg/kg would be expected to result in serious, potentially life-threatening symptoms.

Mechanisms of Toxicity

Cardiac Effects

  • Cardiac sodium channel blockade
  • Delayed rectifier potassium channel (Ikr) blockade
  • Alpha-1 adrenergic receptor blockade

Neurological Effects

  • Central anticholinergic syndrome
  • GABA receptor antagonism
  • Presynaptic amine uptake blockade

Clinical Features

Severe toxicity occurs from sodium channel blockade and may cause arrhythmias, cardiovascular collapse, convulsions and coma.

Anticholinergic Toxicity (Peripheral)

Vital Signs

  • Sinus tachycardia
  • Hypertension (early) → hypotension (late)
  • Hyperthermia
  • Tachypnea → respiratory depression

Physical Examination

  • Hot, dry skin
  • Dry mouth and tongue
  • Dilated pupils
  • Flushed face
  • Urinary retention
  • Decreased bowel sounds/ileus

Central Nervous System Effects

Early CNS Manifestations

  • Confusion, agitation
  • Drowsiness, sedation
  • Ataxia
  • Nystagmus
  • Divergent squint
  • Myoclonus

Severe CNS Toxicity

  • Deep coma
  • Convulsions (may herald cardiovascular collapse)
  • Respiratory depression/arrest
  • Absent brainstem reflexes (deep coma)
  • Increased tone and hyperreflexia
  • Extensor plantar responses

Cardiovascular Features

ECG Abnormalities

  • Prolonged QRS duration (>120 msec) - predictor of seizures and ventricular arrhythmias
  • Prolonged PR and QT intervals
  • Non-specific ST segment and T wave changes
  • Atrioventricular block
  • Brugada electrocardiographic pattern
  • Ventricular tachycardia/torsades de pointes

Other Complications

Emergency Management

Airway Protection First: Patients can deteriorate rapidly. Maintain a clear airway and ensure adequate ventilation.

Initial Stabilization

Primary Survey (ABCDE)
  1. Airway: Protect airway, consider early intubation
  2. Breathing: Oxygen, ventilation support if needed
  3. Circulation: IV access, cardiac monitoring, fluid resuscitation
  4. Disability: Neurological assessment, glucose check
  5. Exposure: Full examination, temperature management

Gastrointestinal Decontamination

Activated Charcoal

  • Consider if patient presents within 1 hour of ingestion
  • Adult dose: 50 g
  • Pediatric dose: 1 g/kg body weight
  • Only if airway can be protected
  • Second dose after 1-2 hours in symptomatic patients

Contraindications

  • Compromised airway
  • Decreased level of consciousness
  • Bowel obstruction/perforation
  • Late presentation (>1-2 hours)

Sodium Bicarbonate Therapy

Indications for Sodium Bicarbonate

Consider immediate administration of 50-100 mL of 8.4% sodium bicarbonate if:

  • QRS duration >120 msec
  • Hypotension unresponsive to fluids

Even in the absence of acidosis

Administration Protocol
  1. Administer 50-100 mL 8.4% sodium bicarbonate IV bolus
  2. Recheck ABG and 12-lead ECG after administration
  3. Give further doses if QRS prolongation persists
  4. Guide by arterial blood gas monitoring
  5. Target pH 7.45-7.55

Specific Complications Management

Metabolic Acidosis

Management

  • Correct hypoxia first
  • Adequate fluid resuscitation
  • If acidosis persists, correct with IV sodium bicarbonate
  • Rapid correction particularly important with QRS prolongation
  • Monitor ABG frequently

Convulsions

Initial Management

  • Give oxygen
  • Check blood glucose, U&Es, calcium, magnesium, phosphate
  • Check arterial blood gas
  • Correct acid-base and metabolic disturbances

Seizure Control

  • First-line: IV benzodiazepines (lorazepam, diazepam)
  • Second-line: Phenobarbital
  • Avoid phenytoin (may worsen arrhythmias)
  • Consider propofol or midazolam infusion for status epilepticus

Hypotension

Stepwise Management

  1. Ensure adequate fluid resuscitation
  2. Treat bradyarrhythmias and tachyarrhythmias appropriately
  3. Consider early critical care referral for fluid-resistant hypotension
  4. Glucagon as treatment option for severe hypotension, heart failure, or cardiogenic shock

Advanced Management

  • Norepinephrine for vasopressor support
  • Consider lipid emulsion therapy
  • ECMO for refractory cardiogenic shock
  • Transvenous pacing for severe bradycardia

Monitoring and Disposition

Monitoring Requirements

  • Continuous cardiac monitoring (minimum 6 hours)
  • Frequent vital signs
  • Serial ECGs (QRS duration monitoring)
  • Neurological observations
  • Urine output monitoring
  • Arterial blood gas monitoring in severe cases

Disposition Criteria

Clinical Status Disposition
Asymptomatic >6 hours
Normal ECG		 Medical clearance possible
Mild symptoms
Stable vital signs
QRS <100 msec		 Extended observation (12-24 hours)
Any symptoms >6 hours
QRS >100 msec
Altered mental status
Hemodynamic instability		 ICU admission required

High-Risk Features Requiring ICU

  • QRS duration >120 msec
  • Recurrent seizures
  • Coma or decreased consciousness
  • Respiratory depression
  • Hemodynamic instability
  • Ventricular arrhythmias
  • Metabolic acidosis

Special Considerations

Pediatric Patients

  • More susceptible to CNS effects
  • Lower threshold for ICU admission
  • Careful fluid management
  • Consider child protection issues

Elderly Patients

  • Increased risk of complications
  • More susceptible to cardiac effects
  • Consider polypharmacy interactions
  • Lower threshold for admission

Pregnancy

  • Maternal stabilization is priority
  • Fetal monitoring if >20 weeks
  • Obstetric consultation
  • Consider teratogenic effects of treatments